1. Field
Provided are an anti-Her3 scFV fragment, an anti-c-Met/anti-Her3 bispecific antibody including the same, and a method of preventing and/or treating a cancer using the same.
2. Description of the Related Art
c-Met and EGFR (or HER family) interact with each other and are involved in various mechanisms related to tumor growth. These proteins (targets) are typical receptor tyrosine kinases (RTKs) present at the surface of cells, thereby inducing the proliferation of cancer cells, the penetration of the cancer cells, angiogenesis, etc. Also, these proteins participate in each other's signal transduction systems by interacting with each other, thereby inducing resistance against each other's therapeutic agents.
In particular, among the EGFR family, Her3 (ErbB3) acts as an important regulator for crosstalk between the c-Met and EGFR families. If resistance to anti-EGFR family or anti-c-Met therapy is developed, Her3 may be activated to exert signal transduction, which may yield unsatisfactory therapeutic results.
Meanwhile, bispecific antibodies targeting two or more antigens have been developed in various kinds and forms and are expected as a new drug antibody having excellent therapeutic effects compared to a monoclonal antibody. Most bispecific antibodies have been developed so that their therapeutic effects on cancers can be increased by recognizing an antigen of cytotoxic cells (killer cells) and an antigen of cancer cells at the same time thus leading to the cancer cells being killed by the cytotoxic cells. However, when considering that research indicates cancer cells themselves can be mutated to proliferate and penetrate, by intracellular ligands or various antigens of the same cancer cells as well as the targeted antigen, it is expected that a bispecific antibody capable of recognizing another antigen of the cancer cells as well as an antigen of the killer cells will be also useful in treating cancers.
In addition, various bispecific antibodies have been developed, but their efficiency was not proven in clinical tests, or deleterious side effects were observed. For these reasons, there were many cases which were not approved by FDA and were not marketed as therapeutic antibodies. Some of the biggest problems include the lack of stability and difficulty in producing the antibodies. In the production of early bispecific antibodies having an IgG form, due to random combination between light chains and heavy chains of antibodies, it was very difficult to separate and purify a desired kind of bispecific antibodies, which becomes an obstacle in the mass production. Also, in case of bispecific antibodies with other than IgG forms, their stabilities as a drug were not verified in fields such as protein folding, pharmacokinetics, and the like.
Accordingly, there is a need for the development of a bispecific antibody which is predicted to achieve effective cancer treatment effects by recognizing two or more kinds of antigens in cancer cells at the same time. Furthermore, there is a need for the development of a bispecific antibody which can enhance cancer treatment as well as address the side-effect and resistance problems of the old drugs.